Research

My lab is interested in the neural circuitry that underlies behavior. Specifically, how does connectivity develop in the young brain and how do mature connections generate behavior?

Brain function relies upon the precise organization of many neural circuits. Although we are beginning to understand important properties of simple circuits, we know little about how complex circuits form and how their mature properties underlie behavior. This is largely because the complexity of most brain circuits prevents their complete examination using traditional labeling or recording methods. Due to the generation of a new powerful approach (“Brainbow”), we can now label populations of cells in many different colors, allowing us to visualize multiple individual components of a complex circuit in unprecedented detail. We have applied this approach to the translucent developing zebrafish nervous system, where individual synapses can be visualized over time within the living animal. Using this combined approach, we are testing how an important circuit within the cerebellum, the mossy fiber-to-granule cell synapse, develops and functions. These studies, along with dynamic imaging and recording of neuronal activity, will allow us to quantify the developmental circuit properties of a complex pathway and begin to determine what types of information are being compared in this pathway to generate appropriate behavior. The combination of two powerful approaches – Brainbow and zebrafish – allows us to ask these detailed questions about a complex circuit in the brain of a living, intact animal.

Our long-term goals are to understand how complex circuits develop and function in the brain. On a broader scale, we hope to shed light upon how the brain controls behavior and how this process can go awry in human disease. There are certain human disorders that arise when normal cerebellar development goes wrong (for example, in childhood cerebellar ataxias). Future directions in the lab will investigate how cerebellar circuits may be perturbed in transgenic zebrafish lines that model human ataxia. A better understanding of normal and abnormal cerebellar circuitry will help broaden our understanding of these diseases, and of the important role that the cerebellum plays in human behavior.